Primary sclerosing cholangitis is a cholestatic disease of the liver characterized by progressive fibrotic
inflammation and obliteration of the extra- and/or intrahepatic bile ducts. There is no effective
therapy. We, therefore, studied the safety and efficacy of
ursodeoxycholic acid in patients with
primary sclerosing cholangitis with or without additional
ulcerative colitis. In a 1-year
ursodeoxycholic acid treatment period, which preceded the controlled study period,
ursodeoxycholic acid was well tolerated in 22 of 24 patients with
ulcerative colitis and in all three patients without
ulcerative colitis. In two patients with
ulcerative colitis the dose of 750 mg
ursodeoxycholic acid/day led to
diarrhea, but following reduction of the dose to 500 and 250 mg/day
ursodeoxycholic acid was well tolerated. After 1 year of
ursodeoxycholic acid treatment, 20 patients were randomly assigned to receive either
ursodeoxycholic acid 750 mg/day or placebo. All of them finished a double-blind, placebo-controlled study period. During
ursodeoxycholic acid treatment, the liver
enzymes improved markedly. The difference in
alanine aminotransferase,
aspartate aminotransferase,
alkaline phosphatase and
gamma-glutamyltransferase between the placebo and
ursodeoxycholic acid group was significant (p < 0.05). Following
ursodeoxycholic acid treatment,
pruritus and
fatigue improved in half of the patients but the difference between the placebo and
ursodeoxycholic acid group was not significant. According to the ethical guidelines, after 3 months of placebo treatment, the controlled study had to be discontinued because of a more than twofold increase of serum
transaminases in 8/10 patients on placebo. After the end of the controlled study, all patients were continuously treated with
ursodeoxycholic acid for up to 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)